Parkinson’s Disease and the Gut Microbiome in Rural California

Abstract

Background: Increasing evidence connects the gut microbiome to Parkinson’s disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features. Objective: We aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features. Methods: In a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16 S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function). Results: PD patients’ gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis. PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. Two genera were associated with motor function. Conclusion: PD patients differed from controls in gut microbiome composition and its predicted metagenome, and their clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease

“…Multiple studies have also linked p-cresol with autism (23)(24)(25) and altered brain dopamine metabolism in neurodevelopment (26). Furthermore, gut dysbiosis has been linked to both PD and autism, including among our own patients (27), with some research even indicating that misfolded a-synuclein retrogradely propagates from the enteric to the central nervous system (28). P-cresol and its' metabolites therefore represent very compelling targets for future mechanistic research.…”

Diet and the gut microbiome in patients with Parkinson’s disease

“…We also stratified analyses by PD duration, as we reported previously that patients with longer disease duration consumed higher amounts of sugars 6 and exhibited differences in microbial abundance with increasing disease duration 21 . Patients with both long (≥10 years) and short (<10 years) PD durations who maintained a healthier diet had an increased abundance of Coprococcus 1 ( q -trend <0.001 for both; p -heterogeneity = 0.160; Supplementary Data 4 ).…”

Metagenomics of the Gut Microbiome in Parkinson's Disease: Prodromal Changes

“…A priori targeted species selected based on association with PD in prior published studies. We focused on species available in our dataset within genera previously associated with PD: Akkermansia , 9,14,26,27,30–32 Bifidobacterium , 10,13,15,18,22,26,31–33 Hungatella , 62 Lactobacillus , 15,23,32 Blautia , 10,15,26,30 Oscillibacter , Prevotella , 9,10,19,22,33 Eubacterium , 9 Roseburia , 10,18,26,30,32 Lachnospira , 18,63 and Faecalibacterium 15,19,26,34 . Based on the distribution among the a priori species considered, species abundance was categorized into tertiles, or binary presence/absence if tertile categorization was not possible due to low abundance.…”

“…In supplemental analyses, to assess whether our data support previously published fundings regarding the microbiome and PD, we examined the association with PD of several targeted species selected based on association with PD in prior published studies. We focused on species available in our dataset within genera previously associated with PD: Akkermansia , 9,14,26,27,30–32 Bifidobacterium , 10,13,15,18,22,26,31–33 Hungatella , 62 Lactobacillus , 15,23,32 Blautia , 10,15,26,30 Oscillibacter , Prevotella , 9,10,19,22,33 Eubacterium , 9 Roseburia , 10,18,26,30,32 Lachnospira , 18,63 and Faecalibacterium 15,19,26,34 . We used multivariable logistic regression to estimate the odds ratio (OR; 95% confidence interval [CI]) of PD according to category of abundance of these targeted species.…”

“…1,8 The role of the gut microbiome in PD has been explored a growing number of studies, which have yielded heterogeneous results, likely due to limitations in study design and microbiome sequencing technology. Abundance of some bacterial genera have been somewhat consistently reported to be increased in PD, including Akkermansia 9,14,26,27,[30][31][32] and Bifidobacterium, 10,13,15,18,22,26,[31][32][33] whereas others were decreased, including Prevotella, 9,10,19,22,33 Faecalibacterium, 15,19,26,34 Blautia, 10,15,26,30 and Roseburia. 10,18,26,30,32 Increased intestinal permeability and inflammation has also been noted in PD.…”